title: Differential effects of quinidine, flecainide, and cibenzoline on anisotropic conduction in the isolated porcine heart.
abstract: BACKGROUND
  Anisotropic conduction characteristics, expressed as the ratio of conduction velocities in the longitudinal (Vl) and transverse (Vt) fiber directions, may play a role in the mechanism of some ventricular tachycardias and is influenced by pharmacologic interventions. Discrepancies exist among the reported orientation-dependent effects of available Class I antiarrhythmic drugs. The aim of this study was to assess the respective effects of quinidine (Class IA), flecainide (Class IC), and cibenzoline (not subclassified) on the anisotropic conduction of porcine hearts, in corroboration of their effects on ventricular action potentials.
  
  
  RESULTS
  We studied the actions of 3 and 10 microM quinidine, 1 and 3 microM flecainide, and 0.3 and 1 microM cibenzoline on Vl and Vt determined from 128 electrograms recorded with a plaque electrode on the anterior left ventricle of isolated perfused hearts (spacing 2.5 mm). Vl and Vt were computed from isochronal maps displaying ellipsoid activation during stimulation from the center of the plaque. The effects on the maximal rate of depolarization (Vmax) of action potentials were obtained from ventricular muscle exposed to the same drugs. Flecainide [1 microM] and cibenzoline [0.3 microM] did not alter Vl and Vt significantly. Quinidine [3 microM] predominantly depressed Vl at rapid pacing rates, but the Vl/Vt ratio was not significantly altered. Quinidine [10 microM] and flecainide [3 microM] reduced Vl and Vt in a frequency-dependent fashion. Conversely, cibenzoline [1 microM] mostly decreased Vl and thus decreased the Vl/Vt ratio and increased the Vl/Vt at all pacing rates. This different effect was not related to a greater depressant effect on Vmax
  
  
  CONCLUSIONS
  Quinidine and flecainide act similarly on the anisotropic pattern of conduction (both drugs increase the Vl/Vt ratio), whereas cibenzoline exerts opposite effects. Orientation-dependent effects are different among Class I antiarrhythmic drugs and may be of importance in their therapeutic efficacy or proarrhythmic potential.
authors.affiliation: Department of Cardiology, University of Lille, France. dlacroix@chru-lille.fr
authors.forename: D
authors.initials: D
authors.lastname: Lacroix
authors.forename: P
authors.initials: P
authors.lastname: Delfaut
authors.forename: M
authors.initials: M
authors.lastname: Adamantidis
authors.forename: R
authors.initials: R
authors.lastname: Cardinal
authors.forename: D
authors.initials: D
authors.lastname: Klug
authors.forename: S
authors.initials: S
authors.lastname: Kacet
authors.forename: B
authors.initials: B
authors.lastname: Dupuis
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D016880:Anisotropy; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002304:Cardiac Pacing, Artificial; D005260:Female; D005424:Flecainide / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D006329:Heart Conduction System / Q000187:drug effects*; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D010496:Pericardium / Q000187:drug effects / Q000502:physiology; D026902:Potassium Channel Blockers; D011802:Quinidine / Q000494:pharmacology*; D013552:Swine
chemical_list: D000889:Anti-Arrhythmia Agents; D002121:Calcium Channel Blockers; D007093:Imidazoles; D026902:Potassium Channel Blockers; D011802:Quinidine; D005424:Flecainide; C032151:cifenline